Sickle cell disease is an inheritable hematological disorder based on a mutation in the β-globin gene of hemoglobin. Upon deoxygenation, this mutated hemoglobin polymerizes and causes a shape change (sickling) of the red blood cell. This change in red blood cells leads to obstruction of blood vessels causing a wide variety of complications such as stroke, pulmonary hypertension, end-organ disease and death.
This deformation damages the membrane of subjects' red blood cells and makes the average life of the red blood cells in the range of 10 to 20 days as opposed to 120 days for normal individuals. As a result, subjects suffer from chronic anemia. These damaged red blood cells have a tendency to adhere to the endothelial cells of the blood vessel, neutrophils and platelets, and thus, obstruct blood flow causing frequent painful episodes called “sickle cell crisis,” damaging organs and impairing bone joints.
In addition to the fatal or potentially fatal complications, there are serious nonfatal complications of sickle cell disease such as pain. The severity of the pain may vary, but normally requires some form of medical attention, and hospitalization may be necessary. Chronic inflammation is one of the complications of subjects with sickle cell disease and studies from our laboratory show that both circulating CRP and IL-6 are elevated in steady-state children with sickle cell anemia.
In the U.S. alone, approximately 70,000-100,000 people suffer from sickle cell disease. Sickle cell disease is estimated to affect one of every 1,300 infants in the general population, and one of every 500 of African descent. Currently, there is no cure for sickle cell disease. The disease is chronic and lifelong. Life expectancy is typically shortened.
Previous patents involving methods of treating sickle cell disease have been focused mainly on the effects of the sickled red cells, as the only symptom of the disease. Traditional treatment includes vitamin and mineral supplements directed at normalizing erythropoiesis, increasing HbF production, maintaining hydration of the red cells and whole body and blood transfusions to supply normal, red cells.
For example, U.S. Pat. No. 4,945,083, issued Jul. 31, 1990 to Christian Jansen, Jr. describes a method for treating or preventing macrocytic-megaloblastic anemia with multi-factor vitamin formulations. Other combination therapies for sickle cell anemia (HbSS) with formulations that include vitamins are described in U.S. Pat. No. 5,626,884, issued May 6, 1997 to Lockett, and U.S. Pat. No. 7,214,709, issued May 8, 2007 to Kimoto et al. Both describe formulations including ascorbic acid (vitamin C).
The only cure for this disease is bone marrow transplant, which is not widely available. Currently, the only medication, which seems to have some efficacy, is an oral administration of hydroxyurea. This compound increases the cellular content of fetal hemoglobin (HbF), which does not polymerize at low oxygen concentration like HbS. However, hydroxyurea has some negative side effects, such as bone marrow suppression, and a life-long administration may not be recommended.
Accordingly, there is a need in the art for the treatment of sickle cell disease or the complications associated therewith. The present invention fulfills these needs and further provides other related advantages.